Influenza, which is also known as “flu”, is a severe infectious disease associated with symptoms ranging from mild to severe and causes an annual world-wide death toll of about 250,000 to 500,000 people. The influenza virus annually affects from about 5 to about 15 percent of the population causing acute respiratory diseases. In particular, young, elderly patients and also patients suffering from chronic diseases are at high risk and in particular may be threatened by accompanying severe bacterial infections like pneumonia.
Influenza viruses can be categorized into three types, namely types A, B and C. The type A influenza virus which is the most likely to cause epidemic or pandemic infections among all other types is further categorized into many subtypes depending on the type of certain viral proteins. Viruses of the influenza A type which are able to cross-infect and recombine between different species are the most virulent human pathogens. Several severe influenza pandemics were caused by this influenza virus type like for example by the subtypes H1N1 (1918, 2009), H3N2 (1968) or H5N1 (2004).
Therefore, early treatment of influenza is vital. Conventional therapies for treatment of influenza include administration of antiviral drugs like neuraminidase inhibitors (oseltamivir and zanamivir) and M2 protein inhibitors (adamantane derivatives) or viral polymerase inhibitors like ribavirin, all of them are associated with more or less severe adverse events and several contraindications or interactions with further drugs need to be considered while the therapeutic benefit might be limited due to a high risk of drug resistance. Moreover, toxicity studies indicated a possible tumorigenic and embryo toxic potential of neuraminidase inhibitors.
Thus, there is a strong need for therapeutically effective compounds and improved ways for successfully treating influenza, especially infections caused by influenza type A. As usual, it is generally desirable to have compounds with reduced risk for side effects, which can be prepared in a cost-effective way.
Recently, Traditional Chinese medicine as well as complementary and alternative medicine has getting popular providing a lot of treatment options. Traditional Chinese medicines based on plant materials as well as plants or respective components gained from plants usually allow for treatment of various diseases and conditions while bearing a reduced risk for side effects. In view of the rich medicinal plant resources, available respective medicines can usually be produced in a cost-effective way. Accordingly, there has been a lot of research with regard to plants and respective ingredients for treatment of several diseases and conditions.
For example, Baphicacanthus cusia (Nees) Bremek is distributed in Southern China and already used as a traditional Chinese medicine named Nan-Ban-Lan-Gen (NBLG) (Ho Y. L. et al., Am. J. Chin. Med. 2003, 31, 61). The nature and taste of this material is cold and bitter, and it is commonly used for treating conditions associated with heat and toxins. It was recorded in the People's Republic of China Pharmacopoeia (2015) as a Chinese herbal medicine for anti-viral treatment and has also been listed as one of the major anti-severe acute respiratory syndrome (SARS) medicines during the outbreak of SARS in 2003.
Till now indigoid indole alkaloids, quinazolinone alkaloids, monoterpenes, triterpenes, flavonoids, sterols, anthraquinones, benzoxazinones, and lignans have been reported to be present in Baphicacanthus cusia (Gu W. et al., J. Nat. Prod. 2014, 77, 2590). The specific structure of the ingredients in Baphicacanthus cusia is not completely known and the number of reports dealing with an isolation of ingredients from Baphicacanthus cusia let alone a successful isolation of those ingredients is limited. Since diversified components in Chinese herbal medicines often act via multiple modes, there is a strong need for identifying and providing components in isolated form with sufficient therapeutic efficiency, in particular with sufficient anti-viral activity such as for treatment of influenza like influenza type A infections caused by H1N1. Having those active ingredients in isolated form could further reduce the risk of side effects or interactions which might limit the therapeutic use due to the presence of further ingredients with reduced or insufficient efficacy for treating the respective disease.